httk: invitro_mc – R documentation

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invitro_mc

Draw in vitro TK parameters including uncertainty and variability.

Description

Given a CAS in the HTTK data set, a virtual population from HTTK-Pop, some user specifications on the assumed distributions of Funbound.plasma and Clint, draw "individual" values of Funbound.plasma and Clint from those distributions.

Usage

invitro_mc(
  parameters.dt = NULL,
  samples,
  fup.meas.cv = 0.4,
  clint.meas.cv = 0.3,
  fup.pop.cv = 0.3,
  clint.pop.cv = 0.3,
  poormetab = TRUE,
  fup.lod = 0.01,
  fup.censored.dist = FALSE,
  adjusted.Funbound.plasma = TRUE,
  clint.pvalue.threshold = 0.05,
  minimum.Funbound.plasma = 1e-04
)

Arguments

`parameters.dt`	A data table of physiological parameters
`samples`	The number of samples to draw.
`fup.meas.cv`	Coefficient of variation of distribution of measured `Funbound.plasma` values.
`clint.meas.cv`	Coefficient of variation of distribution of measured `Clint` values.
`fup.pop.cv`	Coefficient of variation of distribution of population `Funbound.plasma` values.
`clint.pop.cv`	Coefficient of variation of distribution of population `Clint` values.
`poormetab`	Logical. Whether to include poor metabolizers in the Clint distribution or not.
`fup.lod`	The average limit of detection for `Funbound.plasma`, below which distribution will be censored if fup.censored.dist is TRUE. Default 0.01.
`fup.censored.dist`	Logical. Whether to draw `Funbound.plasma` from a censored distribution or not.
`adjusted.Funbound.plasma`	Uses adjusted Funbound.plasma when set to TRUE.
`clint.pvalue.threshold`	Hepatic clearance for chemicals where the in vitro clearance assay result has a p-values greater than the threshold are set to zero.
`minimum.Funbound.plasma`	Monte Carlo draws less than this value are set equal to this value (default is 0.0001 – half the lowest measured Fup in our dataset).
`parameters`	A list of chemical-specific model parameters containing at least Funbound.plasma, Clint, and Fhep.assay.correction.

Value

A data.table with three columns: Funbound.plasma and Clint, containing the sampled values, and Fhep.assay.correction, containing the value for fraction unbound in hepatocyte assay.

Author(s)

Caroline Ring and John Wambaugh

References

Wambaugh, John F., et al. "Assessing Toxicokinetic Uncertainty and Variability in Risk Prioritization." Toxicological Sciences (2019).

httk

High-Throughput Toxicokinetics

v2.0.4

GPL-3

Authors

John Wambaugh [aut, cre] (<https://orcid.org/0000-0002-4024-534X>), Robert Pearce [aut] (<https://orcid.org/0000-0003-3168-4049>), Caroline Ring [aut] (<https://orcid.org/0000-0002-0463-1251>), Greg Honda [aut] (<https://orcid.org/0000-0001-7713-9850>), Mark Sfeir [aut], Matt Linakis [aut] (<https://orcid.org/0000-0003-0526-2395>), Sarah Davidson [aut] (<https://orcid.org/0000-0002-2891-9380>), Miyuki Breen [ctb] (<https://orcid.org/0000-0001-8511-4653>), Shannon Bell [ctb], Xiaoqing Chang [ctb] (<https://orcid.org/0000-0003-0752-1848>), Jimena Davis [ctb], James Sluka [ctb] (<https://orcid.org/0000-0002-5901-1404>), Nisha Sipes [ctb] (<https://orcid.org/0000-0003-4203-6426>), Barbara Wetmore [ctb] (<https://orcid.org/0000-0002-6878-5348>), Woodrow Setzer [ctb] (<https://orcid.org/0000-0002-6709-9186>)

Initial release

2021-05-07